Publication Date:
2005-11-16
Description:
Decitabine, a hypomethylating agent, has clinical activity in imatinib refractory chronic myeloid leukemia (Issa et al. JCO 2005). The objective of this phase II study is to investigate the activity of decitabine in combination with imatinib in patients with Ph-positive CML-AP or non-lymphoid CML-BP. To be eligible for this study, patients who had previously been treated with imatinib must have clinical evidence of imatinib failure. Treatment schedule was imatinib orally at 600mg daily and decitabine intravenously at 15mg /m2 x 5 days/week for two consecutive weeks every 6 weeks. At least two courses were planned for all patients. Global DNA methylation of peripheral blood mononuclear cells was measured using a LINE1 bisulfite/pyrosequencing assay. From January 2003 to July 2005, 27 patients (8 BP, 19 AP) were enrolled into this study. Clonal evolution was observed in 21 patients (77%). Twenty-four patients (88%) had failed prior therapy with imatinib, and 3 (12%) were newly diagnosed patients with CML (2 AP and 1 BP). All patients received at least 1 cycle of the treatment (median 3, range 1–12). Toxicity was evaluated in all patients; grade 3/4 toxicity included infection (n=9), CNS bleed (n=2), GI bleed (n=2), dyspnea (n=1), diarrhea (n=1), and edema (n=1). Seven patients (26%) received only 1 cycle of treatment, owing to early death from acute disease progression (n=5), recurrent subdural hematoma (n=1), and a patient’s decision due to grade 3 diarrhea (n=1). Twenty patients (74%) received 2 or more treatment cycles and were evaluated for response. Nine patients (33%) achieved complete hematologic response (CHR: BM blast
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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